The solubility of glimepiride (GMP) was studied in nine mono-solvents; i.e. water, glycerin, propylene glycol (PG), polyethylene glycol 600 (PEG 600), dimethylacetamide (DMA), dimethylformamide (DMF), dimethyl sulphoxide (DMSO), 1,4-butandiol and ethyl acetate over a temperature range of to at atmospheric pressure . The mole fraction solubility values of GMP in nine different pure solvents were increased with increase in temperature. Solid phase characterization using spectral, thermal and diffraction techniques showed no polymorphic transformations during the experimentation. The highest mole fraction solubility was noticed in dimethyl acetamide ( at ) and lowest in water ( at ). The results obtained were compared by the application of thermodynamic based models such as van’t Hoff equation, Apelblat equation, and Buchowski–Ksiazaczak () equation with values of 6.50, 1.74, 14.15 respectively. In addition, all generated solubility data and the collected data from literature were fitted to a new linear model and two boosting models. Their evaluations demonstrated that the CatBoost model outperformed in interpolation scenarios, while the linear model exhibited the best performance in extrapolating predictions to new temperatures. Activity coefficients () and excess enthalpy (HE) were estimated to understand solute–solvent interactions. The apparent dissolution thermodynamic properties were calculated using van’t Hoff equation and revealed that GMP dissolution was endothermic, non-spontaneous and enthalpy driven. Thus, the solubility data obtained in different solvents will be beneficial for various processes of GMP like purification, synthesis, preformulation, crystallization, and development of different formulations.
